This laboratory has, in the past several months, been much concerned with hormonal factors regulating lipogenesis in mammalian liver as well as in hepatomas of all degrees of differentiation. We have shown that cyclic 3',5' AMP (cAMP) specifically inhibits biosynthesis of cholesterol and de novo fatty acid in liver via a mechanism not yet fully defined; and that this mechanism is totally deleted in at least three varieties of hepatoma. Biochemical indices of Krebs cycle operation are unaffected by the nucleotide. We are now attempting to locate precisely the site(s) of cAMP blockade of lipogenesis, both with regard to sterologenesis and to fatty acid generation. In addition, a systematic search for the hormone(s) (first messenger) responsible will be carried out, together with a study of the nature of hormone receptor sites in liver and hepatoma. This will be done as a part of the broad question of primary hormonal control of lipogenesis in these two tissues. Further, we will determine whether the addition of a factor isolated from liver homogenates can impart cAMP-induced regulatory response to lipogenesis in tumor homogenates, or whether a similar extract from tumor can ablate cAMP lipogenic suppressibility from normal liver.